Introduction to

Cardiovascular

Disorders

Introduction

Cardiovascular disease is the most frequent cause

of adult death in the Western world

Incidence of ischaemic heart disease is rising Asia

Valvular heart disease is common, but the aetiology

varies in different parts of the world

Indian subcontinent and in Africa, it is predominantly

due to rheumatic fever, whereas calcific aortic

valve disease is the most common problem in

developed countries

Functional Anatomy

and Physiology

Anatomy

heart acts as two serial pumps

right heart circulates blood to the lungs where it

is oxygenated

left heart receives this and circulates it to the rest

of the body

atria - thin-walled structures that act as priming

pumps for the ventricles

The interatrial septum separates the two atria

20% of adults a patent foramen ovale is found

RA receives blood from the superior and inferior venae cavae and

the coronary sinus

LA receives blood from four pulmonary veins

ventricles - thick-walled structures, adapted to circulating blood

through large vascular beds under pressure

atria and ventricles are separated by the annulus fibrosus,

forms the skeleton for the atrioventricular (AV) valves

Electrically insulates the atria from the ventricles

LV myocardium is normally around 10 mm thick (c.f. RV thickness of 2–3 mm) because it pumps blood at a higher pressure

normal heart occupies less than 50% of the

transthoracic diameter in the frontal plane, as

seen on a chest X-ray

In disease states or congenital cardiac

abnormalities, the silhouette may change as a

result of hypertrophy or dilatation.

The coronary circulation

left main and right coronary arteries arise from the left and right

coronary sinuses of the aortic root

left main coronary artery divides into LAD, which runs in the anterior interventricular groove, and the LCX, which runs posteriorly in the

atrioventricular groove

LAD - anterior part of the septum (septal perforators) and the

anterior, lateral and apical walls of the LV

LCX - lateral, posterior and inferior segments of LV

RCA runs in the right atrioventricular groove

Supply RA, RV and inferoposterior aspects of the LV

PDA runs in the posterior interventricular groove

supplies the inferior part of the interventricular septum

branch of the RCA in approximately 90% of people (dominant right system)

supplied by the LCX in the remainder (dominant left system).

RCA supplies the SA node in about 60% of and the AV node in about 90%.

Conducting system of the heart

SA node is situated at the junction of the superior vena cava and RA

Specialised atrial cells that depolarise at a rate influenced by the

autonomic nervous system and by circulating catecholamines

annulus fibrosus forms a conduction barrier between atria and

ventricles

Only pathway through it is the AV node - conducts relatively slowly,

producing a necessary time delay between atrial and ventricular

contraction.

His–Purkinje system – comprised of the bundle of His, the right and left bundle branches, anterior and posterior fascicles of the left

bundle branch, and the smaller Purkinje fibres

Nerve supply of the heart

innervated by both sympathetic and parasympathetic fibres

Adrenergic nerves from the cervical sympathetic chain supply

muscle fibres in the atria and ventricles and the electrical conducting system

Positive inotropic and chronotropic effects are mediated by β1-

adrenoceptors

Parasympathetic pre-ganglionic fibres and sensory fibres reach the

heart through the vagus nerves

Cholinergic nerves supply the AV and SA nodes via muscarinic (M2) receptors

Cardiac Ultrastructure

three-fourths of the ventricular mass is

composed of cardiomyocytes

60–140 m in length and 17–25 m in diameter

each cell branches and interdigitates with

adjacent cells.

intercalated disc permits electrical conduction via gap junctions,

and mechanical conduction via the fascia adherens, to adjacent

cells

basic unit of contraction is the sarcomere

striated appearance due to the Z-lines

sarcomere

structural and functional unit of contraction

lies between adjacent Z lines

Within the sarcomere are alternating light and dark

bands - striated appearance under the light microscope

At the center of the sarcomere is a dark band of

constant length, the A band, which is flanked by two

lighter bands, the I bands, , which are of variable length

consists of two sets of interdigitating myofilaments

Thicker filaments, composed of myosin ,traverse the A

band

Thinner filaments, composed of actin course from the Z

lines through the I band into the A band

thick and thin filaments overlap only within the (dark) A

band, whereas the (light) I band contains only thin

filaments

The Contractile Process

Sliding filament model for muscle contraction

With activation, the actin filaments are

propelled farther into the A band

A band remains constant in length, whereas the

I band shortens and the Z lines move toward one

another

myosin molecule - has a rodlike portion with a globular portion (head) at its end

globular portions of myosin form the bridges between the myosin and actin molecules and are the site of ATPase activity

Actin molecule - double helix of two chains of actin molecules wound about each other on a larger molecule, tropomyosin

regulatory proteins—troponins C, I, and T—are spaced at regular intervals on actin

Four steps in cardiac muscle

contraction and relaxation

In relaxed muscle, ATP bound to the myosin head

dissociates the thick and thin filaments

actin binding site is blocked by tropomyosin

Step 1: Hydrolysis of myosin-bound ATP by the ATPase site

on the myosin head

Step 2: Ca2+ binds to troponin C, exposed active sites on

actin

actin interacts with the myosin head to form an active

complex

Step 3: The muscle contracts when ADP dissociates from

the myosin head

Step 4: The muscle returns to its resting state, when a new

molecule of ATP binds to the rigor complex and

dissociates the myosin head from the actin

Cardiac Action Potential

action potential has four phases

Potassium current (IK1) is the principal current during phase 4 and determines the resting membrane potential of the myocyte

Sodium current generates the upstroke of the action potential (phase 0)

activation of IKto with inactivation of the Na current inscribes early repolarization (phase 1)

The plateau (phase 2) is generated by a balance of repolarizing potassium currents and depolarizing calcium current

Inactivation of the calcium current with persistent activation of potassium currents (predominantly IKr and IKs) causes phase 3 repolarization

Cardiac output

Cardiac output is the product of stroke volume

and heart rate

Stroke volume is the volume of blood ejected in

each cardiac cycle

Dependent upon

end-diastolic volume and pressure (preload),

myocardial contractility

systolic aortic pressure(afterload)

Control of Cardiac Performance

and Output

the stroke volume of the ventricle depend on

three major influences

(1) the length of the muscle at the onset of

contraction, i.e., the preload

(2) the tension that the muscle is called on to

develop during contraction, i.e., the afterload

(3) the contractility of the muscle, i.e., the extent

and velocity of shortening at any given preload

and afterload

Determinants of Stroke Volume

Starling's law of the heart

The relation between the initial length of the

muscle fibers and the developed force

prime importance for the function of heart

muscle.

states that within limits, the force of ventricular

contraction depends on the end-diastolic length

of the cardiac muscle(ventricular end-diastolic

volume)

Laplace's law

Afterload is determined by the aortic pressure as well as

by the volume and thickness of the ventricular cavity

Laplace's law states that the tension of the myocardial

fiber is the product of the intracavitary ventricular

pressure and ventricular radius divided by wall thickness

afterload on a dilated left ventricle exceeds that on a

normal-sized ventricle

afterload on a hypertrophied ventricle is lower than of a

normal chamber

Epidemiology of Cardiovascular

Disease

Introduction

Cardiovascular disease (CVD) is now the most

common cause of death worldwide

Before 1900, infectious diseases and malnutrition

were the most common causes and CVD was

responsible for less than 10% of all deaths

Today, CVD accounts for approximately 30% of

deaths worldwide, including nearly 40% in high-

income countries and about 28% in low- and

middle-income countries.

Known as THE EPIDEMIOLOGIC TRANSITION

driven by industrialization, urbanization, and

associated lifestyle changes

taking place in every part of the world among

all races, ethnic groups, and cultures

Three million CVD deaths occurred in high-

income countries in 2001, compared with 13

million in the rest of the world.

Global Trends in Cardiovascular

Disease

by 2001, CVD was responsible for 29% of all

deaths and 14% of the 1.5 billion lost DALYs

By 2030, when the population is expected to

reach 8.2 billion, 33% of all deaths will be the

result of CVD

Of these, 14.9% of deaths in men and 13.1% of

deaths in women will be due to CHD

Stroke will be responsible for 10.4% of all male

deaths and 11.8% of all female deaths

Behavioral Risk Factors

Tobacco

Tobacco currently causes about 5 million deaths—9% of all

deaths—annually.

Approximately 1.6 million are CVD-related

If current smoking patterns continue, by 2030 the global burden of

disease attributable to tobacco will reach 10 million deaths annually

Diet

increase in intake of saturated animal fats and hydrogenated

vegetable fats, which contain atherogenic trans-fatty acids, along with a decrease in intake of plant-based foods and an increase in

simple carbohydrates

Physical Inactivity

The increased mechanization that accompanies the economic

transition leads to a shift from physically demanding agriculture-based work to largely sedentary industry- and office-based work

Metabolic Risk Factors

Lipid Levels

Worldwide, high cholesterol levels are estimated to

cause 56% of ischemic heart disease and 18% of strokes,

amounting to 4.4 million deaths annually

Social and individual changes that accompany

urbanization clearly play a role because plasma

cholesterol levels tend to be higher among urban

residents than among rural residents

greater consumption of dietary fats—primarily from

animal products and processed vegetable oils—and

decreased physical activity

Hypertension

Worldwide, approximately 62% of strokes and

49% of cases of ischemic heart disease are

attributable to suboptimal (>115 mmHg systolic)

blood pressure, which is believed to account for

more than 7 million deaths annually

One major concern in low- and middle-income

countries is the high rate of undetected, and

therefore untreated, hypertension

Obesity

Although clearly associated with increased risk of CHD, much of the risk posed by obesity may be mediated by other CVD risk factors, including hypertension, diabetes mellitus, and lipid profile imbalances

Diabetes Mellitus

worldwide rates of diabetes—predominantly Type 2 diabetes—are on the rise

In 2003, 194 million adults, or 5% of the world's population, had diabetes

By 2025, this number is predicted to increase 72 percent to 333 million

Approach to the Patient with

Possible Cardiovascular Disease

Cardiac Symptoms

symptoms caused by heart disease result most

commonly from

myocardial ischemia

disturbance of the contraction and/or relaxation

of the myocardium

obstruction to blood flow

abnormal cardiac rhythm or rate

Chest pain

Breathlessness

Syncope

Palpitations

Pedal Edema

Fatigue

Diagnosis

As outlined by the New York Heart Association (NYHA),

the elements of a complete cardiac diagnosis include

the systematic consideration of the following

1. The underlying etiology. Is the disease congenital,

hypertensive, ischemic, or inflammatory in origin?

2. The anatomical abnormalities. Which chambers are

involved? Are they hypertrophied, dilated, or both?

Which valves are affected? Are they regurgitant and/or

stenotic? Is there pericardial involvement? Has there

been a myocardial infarction?

3 The physiological disturbances. Is an arrhythmia present? Is there

evidence of congestive heart failure or myocardial ischemia?

4 Functional disability. How strenuous is the physical activity required to elicit symptoms?

New York Heart Association

Functional Classification

Investigation of CardiovascularDisease

Basic tests

electrocardiography,

chest X-ray

Echocardiography

Procedures such as

cardiac catheterisation

Radionuclide imaging,

computed tomography (CT)

Magnetic resonance imaging (MRI)

Electrocardiogram (ECG)

used to assess cardiac rhythm and conduction

provides information about chamber size

main test used to assess for myocardial

ischaemia and infarction.